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USMLE Step 1 – 2025/2026 Q&A Master File | Verified Practice Questions with Detailed Answers (100% Accurate – Clinical & Preclinical Mastery)

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This document is the ultimate Q&A Master File for USMLE Step 1, updated for the 2025/2026 testing cycle. It includes a comprehensive collection of verified practice questions with 100% accurate and detailed answers covering both clinical and preclinical subjects. Topics include pathology, physiology, biochemistry, microbiology, pharmacology, immunology, and foundational concepts in medicine. Perfect for medical students aiming for mastery and a top score on Step 1.

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USMLE Step 1 – 2025/2026 Q&A
Master File
Verified Practice Questions with Detailed Answers | 100% Accurate |
Clinical & Preclinical Mastery

Introduction
This resource contains 70 verified practice questions with detailed explanations from the
2025–2026 USMLE Step 1 exam blueprint. It reflects the latest revisions in the integrated
systems-based curriculum, providing essential knowledge across basic sciences, foundational
clinical reasoning, and high-yield concepts critical for Step 1 success.

Topics Covered:

• Anatomy (Gross, Neuro, Embryology)
• Physiology
• Biochemistry & Molecular Biology
• Pathology
• Pharmacology
• Microbiology & Immunology
• Behavioral Science
• Genetics
• Biostatistics & Epidemiology
• Systems-Based Integration (Cardio, Neuro, GI, Renal, Endo, etc.)

All correct answers are marked in bold and green with concise, high-yield explanations to
reinforce recall and clinical application.

Practice Questions and Answers
Question 1
Question: A 45-year-old male presents with chest pain radiating to the left arm. ECG shows
ST-elevation in leads V1–V4. Which coronary artery is most likely occluded?
A) Right coronary artery
B) Left anterior descending artery
C) Circumflex artery
D) Posterior descending artery
Rationale: ST-elevation in V1–V4 indicates anterior wall myocardial infarction, typically
due to occlusion of the left anterior descending artery, which supplies the anterior left
ventricle and septum.

Question 2
Question: A 20-year-old female has a mutation in the CFTR gene. What is the primary
defect in cystic fibrosis?
A) Increased sodium reabsorption
B) Defective chloride channel
C) Decreased mucus production
D) Enhanced ciliary function

, Rationale: CFTR gene mutations cause defective chloride channels, leading to thick mucus
accumulation in cystic fibrosis.

Question 3
Question: A 30-year-old male presents with fever, rash, and joint pain after a camping trip.
Biopsy shows spirochetes. Which organism is most likely responsible?
A) Streptococcus pyogenes
B) Borrelia burgdorferi
C) Staphylococcus aureus
D) Neisseria meningitidis
Rationale: Borrelia burgdorferi, transmitted by ticks, causes Lyme disease, presenting with
fever, rash (erythema migrans), and joint pain.

Question 4
Question: A researcher calculates the odds ratio of smoking and lung cancer as 4.5 (95% CI:
2.8–7.2). What does this indicate?
A) No association
B) Increased risk with smoking
C) Decreased risk with smoking
D) Invalid study design
Rationale: An odds ratio of 4.5 with a CI excluding 1 indicates a significant increased risk of
lung cancer with smoking.

Question 5
Case Study: A 55-year-old female with type 2 diabetes presents with polyuria and fatigue.
Labs show HbA1c 9.2%.
Question: Which drug class is most appropriate as initial therapy? Select all that apply.
A) Sulfonylureas
B) Biguanides
C) Thiazolidinediones
D) Lifestyle modification
Rationale: Metformin (biguanide) and lifestyle modification are first-line treatments for type
2 diabetes to improve glycemic control and reduce complications.

Question 6
Question: A 25-year-old male has a seizure. Which brain region is most likely involved?
A) Cerebellum
B) Cerebral cortex
C) Thalamus
D) Medulla oblongata
Rationale: Seizures typically originate in the cerebral cortex due to abnormal neuronal firing.

Question 7
Question: A 40-year-old female presents with jaundice and dark urine. Labs show elevated
direct bilirubin. What is the most likely cause?
A) Hemolysis
B) Biliary obstruction
C) Gilbert syndrome
D) Viral hepatitis

Document information

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Type
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